Method of cleaning passageways using a mixed phase flow of a gas and a liquid

ABSTRACT

A method of cleaning surfaces using a mixed phase cleaning mixture of an aqueous solution and a flow of gas sufficient to produce droplets of the liquid which are entrained by the gas for a time sufficient to clean tubing of various lengths and geometries and porous membranes to remove biofilm, debris and contaminants.

This application is a divisional of U.S. application Ser. No. 09/466,714that was filed with the United States Patent and Trademark Office onDec. 17, 1999, and that issued as U.S. Pat. No. 6,454,871 on Sep. 24,2002. U.S. application Ser. No. 09/466,714 is a continuation-in-part ofU.S. application Ser. No. 08/880,662 that was filed with the UnitedStates Patent and Trademark Office on Jun. 23, 1997, and issued as U,S.Pat. No. 6,027,572 on Feb. 22, 2000. The entire disclosures of U.S.application Ser. No. 09/466,714 and U.S. application Ser. No. 08/880,662are incorporated herein by reference.

This invention relates to a method for removing biofilm, debris,contaminants and the like from the surfaces of passageways, includingpassageways which have irregular or complex shapes or whose walls arepermeable, using a mixed-phase cleaning solution.

BACKGROUND OF THE INVENTION

Interior surfaces of passageways such as small-bore tubing, pipes, ductsand the like, which may carry fluids such as liquids, gases, slurries oraerosols, are very difficult to clean and to maintain in a cleancondition. When the flow path is long and narrow, or hard to reach, itis difficult to clean the surfaces by conventional liquid phase flushingbecause such a long, narrow passageway limits liquid flow velocities bycreating a high resistance to flow. As a result, shear stresses whichcould aid in the removal of contaminants from such surfaces are limited.Low flow velocities also limit the usefulness of solvents for the samereasons.

Cleaning of small diameter passageways is also difficult because of thenature of certain types of residues. Fluid passageways which supplywater, even purified water, develop bacterial and fungal growth from thewater on their interior surfaces, as is well known. Bacteria present inthe water strongly adhere to tubing surfaces and then grow laterally,forming what is known as biofilm. Biofilm is apparent to the touch as aslimy film and is composed of both organic residues and the multiplyingmicroorganisms. The bacteria deposit an underlying structural matrixcomprising polysaccharides with some peptide moieties, calcium carbonateand other materials which adhere to the surfaces of the passageways. Anillustrative example is dental unit water line tubing, which carriesrinse water to the mouth of a dental patient. It has been determinedthat, in the absence of any special precautions, this water exiting fromsuch tubing can include as much as one million (1×10⁶) colony-formingunits of bacteria per milliliter of water (CFU/ml). The source has beenshown to be the surface biofilm which sheds bacteria into the flowingwater. The American Dental Association has recommended reduction of thelevel of bacteria present in dental water delivery systems to below 200CFU/ml to be adopted by the year 2000. Thus, these water lines andtubing must be periodically disinfected or cleaned to ensure thedeactivation of viable bacteria and the removal of this biofilm from thewalls of the tubing in order to prevent infection in dental patients.Removal of biofilm from passageways is also necessary for otherapplications, including medical, industrial and food serviceapplications, because such biofilms are the main cause of high bacterialcounts and high levels of endotoxins.

However, removing biofilm from fluid passageways is quite difficult,which makes disinfecting the surface more difficult as well. The biofilmis strongly adherent to passageway surfaces, whether the surface is madefrom natural materials, such as rubber or metals, or synthetic polymericmaterials, such as polyvinylchloride, polyethylene,polytetrafluoroethylene and the like. Treatment with chemical agents,such as disinfectant and biocidal agents, can kill the exposed surfacebacteria and so reduce the contribution of the biofilm to the totalbacterial count. However, these agents do not readily diffuse into theentire thickness of the biofilm. The biofilm protects the remainingviable bacteria which then rapidly multiply. If it happens that all ofthe bacteria are killed, the biofilm structure remains an ideal host fornew bacteria to colonize and grow. Thus these treatments are generallyonly partially effective, and the original levels of viable bacteriareturn quite rapidly. In order to remove biofilm from a surface, inaddition to chemical treatment, some mechanical action is necessary toproduce shear stress or sufficient impact at the surface.

In dentistry, there are applications for cleaning and disinfecting bothtubing and the dental handpiece. The handpiece, which contains anair-driven turbine or other method of driving a drill and other parts,is about six inches long and is detachable. The tubing and otherpassageways inside the handpiece have a ratio of length to insidediameter of about 100. At present the most common sterilizationprocedure is steam autoclaving. However, in addition to the fact thatautoclaving does not actually remove debris from the handpiece, thisautoclaving procedure can be damaging to the turbine and various sealsin the handpiece. For example, the operating rotational speed of adental drill has been found to decrease with the number ofsterilizations performed.

The old method of cleaning dental handpieces is to flush them with wateror a cleaning solution. While this may flush non-adherent biofilm anddebris from passageways, it can be shown that it provides little or noremoval of adherent biofilm and debris such as blood, mucous and thelike. In order to obtain more force behind the liquid flushing,Littrell, U.S. Pat. No. 3,625,231, describes a device utilizingcompressed air to force a quantity of a cleaning and conditioning fluidthrough the passageways of the handpiece. This device primarily usessingle-phase liquid flow as evidenced by the requirement to observe theclarity of the fluid being expelled from the handpiece as a criterionfor cleaning. This method is only slightly more effective than flushingwith water but may be significantly better than flushing with ahand-operated syringe. However, complete removal of adherent biofilm,debris and contaminants will not occur.

Cleaning of instruments, handpieces and the like by spraying with wateror cleaning solutions is also well known. The spray may be generated byan aerosol can or an atomizing device. While this is a useful method ofdistributing a cleaning solution, it does not ensure complete cleaningof adherent debris. Complete cleaning only occurs when the adhesion ofthe debris is overcome by shear stress. Additionally, an effectivecleaning method may act to weaken the adhesive bond between the debrisand the surface to which it adheres to reduce the required stress. Theadhesive strength must be overcome by a significant margin to ensurecomplete cleaning. Total coverage of all surfaces by shear stress isrequired and sufficient mass transfer must be provided to preventloosened debris from shielding unloosened debris. Simple spraying doesnot ensure that these conditions are met.

It can be estimated that prior art techniques which use a total of onlya drop or two of liquid would not provide enough liquid for the surfacearea of a dental handpiece tube to achieve significant re-formation ofdroplets. One or two drops equals tenths of a milliliter. The presentmethod uses a continuous flow for a period of time such that the amountof liquid used for the same purpose would be tens of milliliters, sometwo orders of magnitude higher.

In addition to biofilm, passageways of various medical devices maycontain food particles, particles of various bodily tissues, mucous,saliva, unclotted or clotted blood or blood components, pathogens,macromolecules and the like, which are referred to hereinafter as“debris”. It is also necessary to remove this debris from thepassageways in which it exists. Such debris may even need to be cleanedfrom passageways which are not fluid-carrying passageways in the normaluse of the device, such as where a cable slides inside a sheath orconduit in an endoscope or biopsy device. Infections arising from theuse of endoscopic devices have been reported and traced to theinefficient cleaning and debris removal by conventional methods.

Endoscopes may contain a passageway for use of a biopsy device, as wellas passageways for other purposes. Both the internal passageways and theexterior of the endoscope must be cleaned after each use. The biopsydevice itself also has interior and exterior surfaces which must be keptclean. Guidelines for cleaning gastrointestinal and other flexibleendoscopy units promulgated by the American Society for GastrointestinalEndoscopy and other bodies include a multi-step method for cleaningtubing between uses to prevent cross-infection between patients. First,mechanical cleaning using a brush and a detergent solution is performedsoon after use. The tubing is then rinsed with water and then adisinfection is carried out using a liquid chemical disinfectant such asas a gluteraldehyde solution. The tubing is then rinsed with sterilewater and dried with forced air. However, this method is time-consumingand suffers from inefficiency in removing all pathogens and otherdebris, as well as being subject to variations in technique from oneoperator to another.

In devices such as heat exchangers, there is a need to remove biofilm,algae, mineral deposits or corrosion products, the last two beingreferred to as scale, from their surfaces. Such substances decrease thethermal efficiency of heat exchangers.

There are also applications for the cleaning of fluid passageways whosewalls are permeable. Surfaces which are permeable or porous arefrequently described as membranes. Herein, the term membrane is used todenote porosity and permeability for a surface of any geometry, and mostcommonly a geometry which is of a tubular shape or other shape morecomplex than flat, such as a hollow fiber filter or a hemodialyzer or aspiral wound filter. Applications in which the wall of the fluidpassageway is a permeable membrane include microfiltration,ultrafiltration, kidney dialysis, reverse osmosis and the like. In suchapplications it is necessary to remove from the membrane suchcontaminants as small particles of any undesirable substances, largemolecular weight macromolecules, biofilm, and (in the case ofhemodialyzers) adsorbed serum proteins, blood cells, cell fragments,platelets, salts and other soluble or dispersed blood constituents. Allof these are included in the term “debris”. Cleaning permeable membranesis more difficult than cleaning solid surfaces, because whatever is heldback by the membrane can lodge either immediately at the membraneexposed surface or within the membrane pore structure, with the surfaceswithin the membrane pore structure being more difficult to clean.

At present hemodialyzers are typically re-used up to about 30 times.However, for some patients, who may represent roughly one-quarter ofhemodialysis patients, hemodialyzers clog more quickly and thus can onlybe re-used three or four times. A better method of cleaning anddisinfecting hemodialyzers between uses could extend their useful life,with consequent economic savings, and possibly improve the biologicalperformance of reused hemodialyzers. Even if the improved cleaning onlyextended the life of those hemodialyzers which are presently re-usedthree or four times up to re-use of up to 15 times, the economic savingswould be considerable.

Membrane filters, at present, are cleaned with harsh liquid-phasechemicals and/or large quantities of hot water, including backflushing.Even though such membranes are cleaned at regular intervals, they neverreturn to their original flux levels. Essentially, this constitutes apermanent de-rating of the membrane's capacity.

In all of these applications and geometries, better cleaning methods forpassageways would be useful to more completely and easily remove thebiofilm, debris, contaminants and the like. In any filtrationapplication an improved cleaning method would either extend its membranelife or improve the performance of the processing.

For medical/dental applications a thorough cleaning is a very importantfirst step in disinfecting or sterilizing the equipment. A good initialcleaning makes any subsequent disinfection or sterilization procedureeasier and more effective by reducing the bioburden which has to bekilled during disinfection or sterilization. At present the major formsof sterilization are heat, harsh chemicals and radiation. Some medicaldevices contain materials or components which suffer damage from one ormore of these processes, or there may be times when for other reasons itmay be impractical to use them. Thus improved methods of disinfection orsterilization which stay close to ambient conditions, use benignchemistry, and are simple to perform would be broadly useful for manymedical and industrial applications. Thus, improved methods of cleaningregular and irregular surfaces and passageways of various medicaldevices, as well as devices in contact with food or potable water, orthose that need to be made sterile, methods that can be carried outrapidly, effectively and inexpensively, and that do not employ extremetemperatures, harsh or toxic chemicals or radiation, would be highlydesirable.

SUMMARY OF THE INVENTION

In accordance with the method of the present invention, a mixture of gasand a suitable liquid, preferably including one or more cleaning agents,is used to create a mixed-phase flow along a surface, which createsshear or impact stresses or similar conditions sufficient to removebiofilm, debris and contaminants from their surfaces. The cleaning agentis commonly a surfactant, but may also be or include an oxidizing agent,an alcohol, a non-surfactant detergent or a solid material. The methodmay be applied to passageway geometries of considerable complexity,including surfaces made of a porous membrane. It further includesoptimally varying parameters such as the fluid mechanics regime of themixed-phase flow, the chemistry of the cleaning liquid, temperature,and, in the case of membranes, the direction, magnitude and sequencingof pressure differences across the membrane.

BRIEF DESCRIPTION OF THE DRAWING

FIG. 1 shows a map of regimes of two-phase fluid flow in a horizontalorientation.

FIG. 2 illustrates an annular geometry that can be cleaned with thepresent methods.

FIGS. 3A and 3B illustrate the geometry of a biopsy device that can becleaned by the method of the invention.

FIG. 4 illustrates a dental handpiece that can be cleaned by the methodof the invention.

FIG. 5 illustrates a shell-and-tube geometry of various devices that canbe cleaned according to the present method.

FIG. 6 illustrates the surface geometry of a permeable membrane that canbe cleaned by the present method.

FIG. 7 illustrates another tubular filter design for ultrafiltrationwhich can be cleaned by the method of the invention.

FIG. 8 illustrates a spiral-wound membrane filter cartridge which can becleaned by the method of the invention.

DETAILED DESCRIPTION OF THE INVENTION

The present invention is directed to a method of cleaning variousirregular surfaces and passageways. Typically the surface or passagewayis long and narrow; it can be of a complex shape; and it can bedescribed by the ratio of its length to width or diameter. Thepassageway may or may not carry fluid during normal use, but it iscapable of carrying mixed-phase fluid flow during the cleaningprocedure. A mixed-phase flow is passed along the surface to dislodgeand remove various materials such as biofilm and other forms ofbiological and non-biological debris and contaminants.

The term “biofilm” as used herein denotes bacterial colonies that growon a surface, and their associated organic matrix materials.

In order to describe the present invention, it is helpful first todiscuss some background information about fluid mechanics, geometry andchemistry. It is known that in order to remove biofilm from a solidsurface, a local shear stress, generally of 53 Pa or more, is required.The difficulty of removing biofilm from a surface can vary with the ageof the biofilm and the nature of the surface, generally becoming moredifficult as the biofilm gets older. It can also depend on the specificbacteria which produced the biofilm. When conventional cleaning using asteady flow of liquid solutions is carried out in a long narrowpassageway, which results in an overall pressure drop along thepassageway, it is likely that the velocity would be quite small and theresulting wall shear stress would be too low to remove biofilm, debrisor contaminants. If the same passageway were cleaned with a steady flowof a gas alone, the gas velocity could be much higher for the sameoverall pressure drop, but sufficient wall shear stress still could notbe obtained because the viscosity of the gas is low.

In fact, for constant-cross section steady flow of any incompressiblesingle-phase fluid, the achievable shear stress can be calculated from acontrol volume view with no reference at all to specific fluidproperties. In any given application there is some limit on the overallpressure drop from one end of the passageway to the other. This may bedetermined by the structural limits of the passageway wall or otherdevice, or the desired overall pressure drop may be equal to thepressure available from pressure sources such as a typical compressor.The pressure range for which compressors are most readily available isapproximately 100 psig. The force on the control volume is given by theoverall pressure drop times the passageway cross-sectional area, and itis also given by the wall shear stress times the wall surface area. Fora given allowable or desired pressure drop across a passageway, the wallshear stress is simply the pressure drop times the cross-sectional flowarea divided by the total wall surface area. For circular tubes thisfurther simplifies totau=deltap/(4*L/D)where tau is the shear stress at the wall, deltap is the pressure dropfrom inlet to outlet of the passageway, and (L/D) is its length todiameter ratio. Thus, the ability to produce a desired shear stress isnot dependent on the fluid properties, or even on whether the fluid is aliquid or a gas. For long narrow tubing (large L/D) this shear stress istoo small to achieve removal of biofilm. For typical conditions, usingthe above formula, the pressure drop might be 14.7 psi (100,000 Pa), andthe L/D might be 1000 or more. This gives an average shear stress of 25Pa, which is not enough to remove biofilm by itself, although it can bea contributing factor.

Cleaning, disinfecting and sterilizing can also be defined here.Cleaning refers to physically removing biofilm, debris and contaminantstypically including bacteria and/or spores. Disinfecting refers tobacterial count, and specifically the reduction in bacterial count by asubstantial fraction (at least six) orders of magnitude), although it isnot necessarily perfect removal of every bacterium or spore.Sterilization refers to inactivating all microorganisms includingbacterial spores.

The flow rate of a gas can be reported in standard volume units per unittime, which is really a mass flow rate and is constant everywhere alonga steady-state flow to which nothing is added or taken away. Standardvolume units such as standard cubic feet are defined at one atmosphere(absolute) of pressure and 0° C. The flow rate of gas can also bereported in actual volumetric units per unit time, which essentially isa geometric quantity based on the local velocity and cross-sectionalarea. This quantity depends on the absolute pressure of the gas at thesite where the measurement is made, because the density or specificvolume of gas depends on the absolute pressure. Therefore, inexperiments such as the present ones, the gas flow rate in actual volumeunits will be different at different places along the flow path.

The mixed-phase flow has a high volume ratio of gas to liquid andcertain combinations of liquid properties. The advantage of amixed-phase cleaning system is that it combines the best of both liquidand gas flow. It can have an overall pressure drop per unit length whichis acceptably small as governed mostly by the characteristics of the gasflow, but the liquid phase is moving with the gas at a substantialvelocity. Therefore, at the places where the liquid phase interacts withthe wall there can be high-velocity impact of the liquid in certainplaces and an accompanying high local shear or impact stress.

A droplet impact can produce a local instantaneous shear stress which ismuch larger than the average shear stress given by the calculation forsingle-phase flow. It can do this because its velocity can be close toor equal to the velocity of the gas, while the shear or impact stress itproduces is related to the liquid viscosity and/or density, both ofwhich are much higher than those of the gas. Thus the mixed-phase flowcombines the best feature of the liquid, its high viscosity and density,with the best feature of the gas, namely the ability to achieve highvelocity without excessive pressure drop per unit length.

The area of the wall cleaned by the impact of any one droplet or liquidfilm is limited, and at any instant of time, the area of the wall beingcleaned is only a fraction of the total wall surface. However, when theprocess is continued for an appropriate period of time, given thegenerally random nature of the process, eventually every bit of theentire surface will experience a significantly large shear stress atsome point in time and will be cleaned. Instead of experiencing acontinuous shear stress, which is too small to do anything to thebiofilm, debris and contaminants, each individual piece of the surfaceexperiences for some, albeit brief, period of time, a much larger shearstress which does remove biofilm, debris and contaminants. However,since at any instant of time these interactions affect only a smallportion of the wall surface, they do not cause a large overall pressuredrop.

A further enhancement of cleaning action can be obtained by includingsolid particles in the liquid. Appropriate chemistry of the cleaningsolution can also be helpful. The liquid cleaning solution is mostcommonly an aqueous solution, but it could also be another liquid. Thegas is generally air, but any other gas can be used.

In a dispersed drop flow regime, when droplets impact the walls of thepassageway, they spread out and form a sheet or liquid layer on thewall. In the fluid flow regimes which are desirable for cleaning, thesheet of liquid (on the wall or surface of the passageway exposed to themixed-phase flow) may attain a thickness such that the moving gas canpull droplets away from the liquid layer. This is called entrainment.Entrainment depends on certain fluid properties and on the creation ofhydrodynamic instabilities in the liquid layer. The instabilities aresuch that when a disturbed shape is created on the surface of the liquidlayer, the liquid surface does not return to flat, but rather furtherdeforms until drops are formed and ripped off. It is believed that whendrops are ripped off, there may also be a force exerted on particles ofbiofilm, debris and contaminants at the place of departure of thenewly-formed droplet. This force acts to detach and remove the biofilm,debris and contaminants from the surface to which they are adhering. Itmay be that the surface tension of the liquid helps to generate thisforce as a droplet is being removed from the surface.

For example, if a particle is wetted relatively fully on one side, whileon the opposite side it is relatively dry, a force can be expectedpulling away from the dry side toward the wet side. For certaincombinations of wetting underneath a particle, and partial dryness ontop of a particle, a force can be expected tending to lift the particleaway from the surface. Since these forces are proportional to surfacetension, this may be a reason not to pursue minimizing surface tensionto extremely small values, and, in fact, the surface tension for watercontaining various salts can be slightly larger than that of pure water.However, surface tension which is somewhat reduced compared to purewater does promote the formation and ripping off of droplets from theliquid layer, which is good. When surfactants are used, they frequentlyhave beneficial detergent effects.

There are also regimes found to exhibit good cleaning in which the flowis film flow, such as suds. As the flow moves, there is a continuousmotion of and folding, stretching and regeneration of films. It isbelieved that when a film slaps into the wall as it moves, there may bean impact force analogous to that of droplet impact, and when a filmpulls away from the wall or moves away from a particle of biofilm,debris or contaminant, there may be a removal force analogous to thatjust described.

Two-phase liquid-gas flow in tubes has been studied in such fields asboilers, electrical generating stations, chemical process plants, andpipelines. Knowledge tends to be somewhat empirical. There are variousnamed regimes of liquid-gas flow such as bubbly, slug, plug, stratified,annular, entrained, froth and mist, with slightly vague demarcationsbetween regimes. However, two variables have emerged as being mostinfluential in determining the flow regime, and they have been used tocreate parameter maps which can be used to approximately predict regionsfor each flow regime. Such maps tend to be specific to one floworientation, such as horizontal, vertical upflow, vertical downflow andthe like. These two major variables are the volumetric ratio of gas toliquid, and the overall velocity.

FIG. 1 is such a map for horizontal flow, which is a typical orientationfor medical and other applications where the present invention would beused. At low velocities and at small gas fractions, there tends to bedistinct regions of gas, i.e., bubbly or stratified or slug, which maybe described as gas dispersed in liquid. At higher gas-to-liquid ratios,the flow is no longer bubbles of gas surrounded by liquid, but ratherbecomes drops of liquid surrounded by gas (liquid dispersed in gas).Also, as the velocity becomes relatively large, droplets are broken awayfrom liquid surfaces on the wall and are carried away (entrained). Theregimes of interest for purposes of cleaning and disinfecting areregimes which occur at relatively low volume fractions of liquid (i.e.,mostly gas on a volume basis) and at high velocity.

In addition to mechanisms such as the forces generated by surfacetension, bubbles can be formed in the liquid, preferably near or atparticles needing to be removed. One way to form bubbles is for gas tobe dissolved in the liquid to come out of solution. Another way is to agas by a chemical reaction.

In the case of a dissolved gas, a useful gas is carbon dioxide becauseit is relatively soluble in water. However, air can be used as well. Thesolubility of any gas in water is dependent on the absolute pressure towhich the solution is exposed; thus a decrease in pressure can cause agas to come out of solution and form bubbles. As liquid flows through apermeable membrane, depressurization occurs. On the upstream side of themembrane, at the higher pressure, a certain concentration of gas canstay in solution in the liquid. On the downstream side of the membrane,which is at a lower pressure, a smaller amount of gas can stay insolution, and the rest comes out of solution as bubbles. The bubblesform directly within the pore structure, where debris needs to beremoved, and thus the debris is dislodged. The debris may serve asnucleation sites for the formation of bubbles. This is an efficient useof dissolved gas in a liquid. Two other gases which are significantlysoluble in water are sulfur hexafluoride and nitrous oxide, although allgases are soluble in water to some degree. If oxygen or ozone is presentin the gaseous phase, an oxidative or disinfectant effect can occur.

It is also possible to create bubbles from aa liquid by means of achemical reaction which forms carbon dioxide or some other gas. Forexample, sodium bicarbonate can react with any acid, such as aceticacid, to form carbon dioxide. In such case the solutions which react toform a gas should not be mixed until they reach the place where bubbleformation is desired.

Another way to create bubbles is by formation of vapor from the liquid.When the liquid is introduced into the passageway to be cleaned, it canbe single phase, near its saturation condition. Then as the liquid flowsthrough the passageway, the thermodynamic conditions would be changed tofavor the existence of two phases, decreasing the pressure. Thispressure decrease, due to the mixed phase flow progressing along thepassageway, can also serve to liberate increasing quantities ofdissolved gas as the flow continues, thereby providing bubble formationalong the entire length of the passageway. Non-continuous pressurevariations, such as surges, can be employed.

Although bubble formation has been described above for porous membranes,they are also applicable for cleaning nonporous applications, e.g.,passageways with solid walls. The pressure drop that promotes bubbleformation is the pressure drop which normally occurs due to flow alongthe principal direction of the passageway.

For the present cleaning method to be successful, one needs tounderstand the mechanisms of formation and re-formation of droplets. Inthe regime of entrained droplet flow (mist), droplets continually formand re-form as the mixed phase flow progresses down a passageway. Afterdroplets strike or are deposited on a surface, liquid is eventuallypulled out of the liquid layer to form new droplets, and the same actionis repeated. In the lowest range of gas velocity, when gas flows past aliquid layer on a flat surface, the surface of the liquid willessentially remain flat and the liquid will be pulled along by shear.This is shown in FIG. 1 as stratified flow.

At somewhat larger gas velocities, waves will appear on the surface ofthe liquid layer as a result of the gas motion. This is shown as thewave regime. At still larger gas velocities, the amplitude of the wavesbecomes large enough that the shape of the surface becomes unstable,which is a hydrodynamic instability similar to the Rayleigh instability.This results in the breaking off of droplets which are then carried awayby the flowing gas. This produces mist and is referred to asentrainment, and is also shown in FIG. 1 as the wave plus mist regime.As shown in FIG. 1, it exists at a mixture velocity of about 10 m/s upto about 40 m/s. The boundaries depend on local conditions and on fluidproperties such as surface tension, viscosity and the like, but suchmaps have only been generated for a limited range of dimensions forcommon fluids such as watyer and occasional hydrocarbons, encompassingonly a narrow range of fluid properties.

The annular-mist regime generally exists at a mixture velocity of over40 m/s, up to about 100 m/s. Presumably in the wave plus mist regime,there is sufficient agitation to form mist, but there still is someliquid collecting on the bottom of the horizontal tube. In the annularmist regime, which is at the highest velocity, there is so muchagitation that there is not much differentiation between the bottom ofthe horizontal tube and other portions of the tube wall. These mistregimes are favorable regions of operation for the present invention. Inthese regimes, the gas velocity is large enough to remove droplets froma liquid layer, and also the velocity of liquid droplets when movingwith the gas is large enough that, upon impact, these droplets arecapable of dislodging or eroding biofilm, debris and contaminants.

The present cleaning method is applicable to extremely long 1/D tubing,and it is especially useful to be able to re-form droplets on acontinuing basis after the initial impact of droplets with the tubingwall. The ability to clean long lengths of tubing is a significantadvantage of the present invention. This requires operating in theappropriate region of parameter space so that the gas is able to formand entrain droplets repeatedly by means of the hydrodynamicinstability. It can be estimated that prior art techniques which use atotal of only a drop or two of liquid would not provide enough liquidfor the surface area of a dental handpiece tube to achieve significantre-formation of droplets. One or two drops equals tenths of amilliliter. The present method uses a continuous flow for a period oftime such that the amount of liquid used for the same purpose would betens of milliliters, some two orders of magnitude higher.

Additionally, some geometries which are capable of being cleaned by thepresent invention have abrupt changes of geometry such as right-angleelbow or U-bends. It might be expected that at such changes ofdirection, many of the droplets will impact the elbow or bend andcoalesce, which presents a danger of depleting the population ofdroplets which are the supposed mechanism of erosion. Nevertheless, itwill be shown hereinbelow that good cleaning using the method of thepresent invention has been observed in passageways which have as many asseven reversals of direction. This indicates that the appropriatemixed-phase flow condition re-establishes itself quite well within ashort distance after such a disturbance.

The formation and re-formation of droplets is influenced by, among otherparameters, the surface tension of the liquid, the viscosity of theliquid, and the velocity of the gas relative to a liquid layer on thewall. In regard to surface tension, it is believed that, particularlyfor small diameter tubing, it is important that the liquid have a lowersurface tension than pure water, which is about 72 dynes/cm. Theaddition of typical surfactants can lower that value to as low as 17dynes/cm, depending on the specific surfactant added and itsconcentration. It is believed that a surface tension lower than about 72dyne/cm, but higher than about 17 dyne/cm, encourages the formation ofan appropriately small droplet size. It is believed that such a sizeresults in high localized shear stresses when a droplet moving at ornear the gas velocity in the principal direction of motion makes contactwith the stationary wall and exerts a viscous shear on the wall. Such avalue of surface tension may also extend the region of shear byencouraging wetting of the wall, and it is believed to help in reformingdroplets after initial impact with the wall. However, if the surfacetension is rather large and the diameter of the passageway is small,slugs may form, see FIG. 1, a regime which does not achieve goodcleaning. It has been discussed elsewhere that surface tension higherthan that of pure water (even as high as 150 dynes/cm) can be achievedwith certain additives and this may be desirable for one mechanism ofremoval of particles. It is believed that the surface tension which isbest used for comparing to the values just discussed is the dynamicsurface tension of the liquid at the time scale characteristic of thedroplet formation processes, rather than the static surface tension. Forsome substances, static and dynamic surface tension areindistinguishable, but for other substances they are different.

A cleaning solution can be used without the addition of a surfactant,providing its surface tension is within the above parameters.

It is also believed that an extremely small surface tension is notdesirable because the droplets might become too small. In such case thedroplets follow the motion of the gas so completely that the droplets donot often impact the surface of the passageway to be cleaned, referredto as channelizing the flow. Thus that amount of surfactant is addedthat provides good cleaning both by virtue of re-forming of droplets anda requirement that the droplets follow the gas motion closely, but nottoo closely.

The viscosity of the liquid is also important. The viscosity of water isaffected by additives, most additives acting to increase the viscosity.Too large a liquid viscosity may prevent the liquid from breaking upinto sufficiently small droploets, and will result in the liquid stayingattached to the wall after the first impact, which is deleterious tocleaning. We have found that 500 centipose (cp) is too viscous.

The volumetric ratio of gas and liquid is also important for achievingcleaning. As will be described hereinafter, typical ratios of gas(usually air) to liquid cleaning solution are 50:1 to 6000:1, with thatratio being considered to be the flow rate of gas at standardconditions, i.e., one atmosphere (absolute) of pressure and 0° C.,relative to the volumetric flow rate of the liquid solution. If too muchliquid is present, the regime of slug flow occurs, and it is difficultto achieve sufficiently high velocities and to achieve droplet formationand ripping off of droplets from the liquid layer on the wall. Toolittle liquid cannot achieve good cleaning in a reasonable period oftime, simply because there are not sufficient droplets to impact thewall often enough. This could in principle be overcome by lengtheningthe treatment time, but at the expense of convenience. For a givensource pressure, the flow rate of gas can be measured when only gas isflowing through the surface being cleaned. At the same source pressure,the flow rate of gas for mixed-phase flow is measured by placing theflow meter upstream of the mixing point. It is usually found that forconditions conducive to good cleaning, the gas flow rate for the mixtureis at least 40% of the flow rate of dry gas alone.

Because the liquid droplets have a larger velocity near the exit thannear the entrance of a passageway, the cleaning effectiveness is usuallybetter near the exit and somewhat less efficient near the inlet, asinfluenced particularly by the velocities of droplets and the effect ofdroplet re-formation and the shear due to the gas flow itself.

It is believed to be advantageous if the main flow of the gas isturbulent. Turbulence in the gas enhances the ongoing reformation of theliquid droplets and also enhances the impact of droplets against thewall by providing, by means of the random turbulent fluctuations oflocal velocity, a velocity component perpendicular to the wall whichdirects the droplets into the wall. In general, turbulence in asingle-phase fluid occurs at a Reynolds number above about 2000 or 3000.Since in the present invention the volume fraction of liquid will berather small, the existence of turbulence can be estimated by theReynolds number for the gas flow. There are some applications where itis unlikely that a gas Reynolds number in the turbulent range can beachieved, primarily because the diameter or characteristic dimension ofthe passageway being cleaned is small. This is the case, for example. inhemodialyzers and perhaps in other hollow fiber filters. In theseinstances, it has been observed that satisfactory cleaning still occurseven at a Reynolds number of several hundred. This implies that,although turbulence is helpful, the most important requirements areprobably a sufficient velocity of the gas combined with the appropriategas/liquid ratio and the appropriate chemistry.

In this case, a gas velocity or Reynolds number as large as reasonablyachievable is desirable, since the velocity would still be significantlylarger than a velocity achievable with water, or similar liquid, alone.In low Reynolds number flows, droplets may interact with the passagewaywalls that are not straight, or because at small passageway diameters,droplets may be a substantial fraction of the passageway diameter andmay reach the surface simply because of size. Also, even though theoverall flow would be laminar, it still may be possible to achieve someuseful local velocity fluctuations at entrances, through the use ofunsteady flow situations, such as by pulsating flow and the like.

A pulsating flow is an alternately stronger flow and weaker flow in agiven direction, or could even involve repeated stopping or reversing ofthe direction of flow. Such disturbances or irregularities orunsteadiness may cause fluctuations in the gas flow which can be usefulin causing localized secondary flow, or unsteady flow, which causesdroplets to interact with the surface to be cleaned. Dropletsinteracting with the surface should provide the shear stress needed tocompletely clean the surface, as long as they have reasonable velocityand sizes. It may also be that in such situations, removal of debris isachieved to a significant degree by the ripping off of droplets from theliquid layer as described above.

The pulsating gas flow can also be turned completely on and off; duringthe off periods, the liquid flow continues. Thus some extra liquidaccumulates inside the passageways during the off periods, and whenpressure is re-applied, there is a surge of flow as the fluid containinga higher liquid fraction is rapidly accelerated. This surge will cleandebris that may already be partially dislodged.

Over the course of several minutes of treatment to remove biofilm,debris and contaminants, the removal rate is slow at the beginning.However, the attachment of the biofilm, debris and contaminants to thesurface is being weakened. Eventually, some biofilm, debris, andcontaminants come off, and this assists in the removal of neighboring orconnecting biofilm. This is particularly true of blood clots, The dragof the fluid, particularly in a surge mode, will in turn transmit aforce to a part still attached and pull it from the surface. In allcases, the removal of some part exposes new surfaces and edges ofbiofilm which can then be removed, or the mixed phase flow can penetrateunder the edge, and begin removal of the biofilm, debris andcontaminants.

At least for some applications, the optimum method may be an essentiallysteady flow of mixed phase flow for most of the cleaning period,followed by the above-described pulsating flow for a portion of thecleaning time.

In addition to the just-described mist regime, the regime of film flowor foam is useful for cleaning, even though such a flow contains perhapsno droplets at all, but rather a multiplicity of films such as are foundin soap bubbles. Film flow is essentially a large number of interactingfilms (which might also be terms suds) being pushed through apassageway. When film flow progresses down a passageway, there isbelieved to be an ongoing process of films bursting or striking the wallor being absorbed onto the wall and new films being regenerated by thestretching or rearranging of existing films. This can act to removebiofilm, debris and contaminants, especially if the film flow is pushedthrough at a substantial velocity. Foam is essentially film flow whichis relatively thick, or has a relatively large apparent viscosity,generally having a smaller fraction of gas and a larger fraction ofliquid. If a foam has an apparent viscosity which is so large that it isdifficult to push the foam through a passageway at any significantvelocity, little cleaning is accomplished. However, if the foam is thinenough (low volume fraction of liquid compared to gas) that it can beforced through passageways at a velocity useful for cleaning, cleaningwill be successful. Also, even a foam which is too thick to be usefulfor cleaning can be useful for soaking. Perhaps the reason why film flowor a little bit of foaminess is useful for cleaning is because the filmor foam counteracts the tendency of some flows to channelize, bycatching droplets. Thick foam can be thought of as resembling shavingcream, while film flow or light foam is more desirable for the presentinvention.

It can also be realized by observing a mixed-phase cleaning flowpropagate through a clear plastic tube, that there need not be a sharpboundary between the droplet flow regime and the film flow, or foamregime. Rather, there can be a gradual progression, with the flowstarting out as droplets and becoming more like film flow or foam as itprogresses along the passageway. Distinguishing between the physicalproperties of regimes is not always clear-cut because there can beregions where the flow is not clearly in either the droplet flow regimeor the film/foam regime. Flows can even be unsteady and alternatebetween the regimes. Foaminess is also influenced by antifoaming agents.In order to achieve good cleaning, conditions appropriate to mist flowis used; for example, high gas velocity is still important.

If the gas velocity cannot achieve 10 m/s identified on the two-phaseflow map as the boundary for mist flow in horizontal two-phase flow,cleaning can be possible anyway. For example, using a hemodialyzer,cleaning was attempted in the vertical direction, and a useful amount ofcleaning was accomplished. It is possible that some geometricorientations are more tolerant of low gas velocities than others. It canbe estimated that successful cleaning applications can involve gasvelocities as low as 1 m/s.

It is also believed that if there are local fluctuations of pressure,gas may enter between the biofilm and the solid surface during a time ofhigh pressure and then, when the pressure is low, may expand and tend tolift up the biofilm, thereby breaking it off. To achieve this, it ispossible to provide pulsating flow. In some regimes of two-phase flow,the fluid behavior is naturally unsteady and this would provide somepressure fluctuations. In addition to the breaking off of biofilm,debris and contaminants, the overall flow flushes the broken-offbiofilm, debris and contaminants out of the passageway.

In addition to passing mixed-phase flow through the passageway,additionally soaking the passageway for a period of time to soften thematerials to be removed may be helpful. In such case, the liquid or foampresent in the passageway is either stationary or only moving slowly. Itmay also be useful to use a sequence of cleaning, soaking and cleaningagain. In addition to cleaning of solid surfaces which has just beendescribed, the present invention can also be used with membranes, whichhave porosity and for which biofilm, debris and contaminants can lodgewithin the pore structure as well as on the overall surface.

In conventional cleaning, many porous passageways can be cleaned bycausing a pressure difference across the membrane so that the pressureon the non-contaminated side is greater than the pressure on thecontaminated side (referred to as backflushing). In this way, debris canbe forced out of the pores back to the surface from which it entered.This technique can be advantageously used with the present inventioninvolving mixed-phase flow in that particles of biofilm, debris andcontaminants may be forced out from their locations within the pores bythe pressure difference of backflushing and be forced into themixed-phase flow and then immediately be removed by the flowingmixed-phase flow.

There are other combinations of flow conditions which can result incleaning according to the present invention, as long as there is mixedphase flow on the side of the membrane which contains the biofilm,debris and contaminants. For example, the lumen side of the membranecontaining the biofilm debris and contaminants can be exposed to a mixedphase flow and the other side of the membrane can be exposed to a higherpressure of either liquid similar to what has already been described, ora gas, either of which would serve to push biofilm, debris andcontaminants out from the direction from which the came into the pores.Under the same conditions of mixed phase flow inside the lumens, thedialysate side of the membrane may be left unpressurized and somecleaning will be achieved, although this method is not as desirable.

Another sequence which may be useful is cleaning with the flow in onedirection, and then reversing the inlet and the outlet and performingthe cleaning procedure with flow in the opposite direction. It has beenpreviously described that cleaning may be somewhat more efficient nearthe outlet of a long tube than it is near the inlet, because of thelarger gas velocity near the exit. In this way, each end of the tubingis the exit end for some period of time, and so experiences the bestcleaning. However, this does increase the cleaning time.

Another example when cleaning in both directions might be particularlyuseful, is the shell side of a shell and tube geometry such as a heatexchanger, a hemodialysis cartridge or ultrafiltration cartridge, wherethe geometry forms a dead end and has a high irregularity because of thelarge numbers of fibers entering the end cap. It is believed thatcleaning of a dead-end may be more effective with flow directed into thedead end and leaving through a branch, as contrasted with the oppositedirection of flow. It is believed that the former flow would create moreturbulence which enters the dead end region and creates a scrubbingaction. Since there are two dead ends (one at each end of the device) itwould probably be advantageous to flow first in one direction, and thento reverse flow and flow in the other direction. In regard to dead-ends,depending on the design of the device, it may be possible to design aconnector which advantageously directs flow into the dead end.

It may be desirable to perform the mixed-phase cleaning procedure of theinvention first for a period of time with one cleaning solution and thenfor a period of time with another cleaning solution. In particular,typically in medical practice, a first step performs a more mechanicalstep of cleaning so as to remove gross amounts of biofilm, debris andcontaminants, and a second step performs a more germicidal step whichmay be chemical, thermal and the like. It is possible to perform bothtypes of steps with mixed-phase flow. If it is desired that the processbe identifiably distinct as to the steps, the more mechanical step ofremoving gross amounts of biofilm, debris and contaminants can beperformed using mixed-phase flow with a liquid cleaning solution asdescribed above, and the other step using mixed-phase flow carried outusing a germicidal cleaning solution. This last cleaning solution caninclude oxidizing agents, biocides or an alcohol. Another example whensequencing of liquid cleaning solutions is desirable is when the debristo be removed is of more than one type, such as both organic debris andinorganic scale, such as calcium carbonate and the like. For organicdebris, an alkaline cleaning solution is preferable, while for inorganicscale, an acidic cleaning solution is preferable. These solutions areapplied sequentially.

Finally, it may be desirable to provide the liquid cleaning solution, orthe gas, or both, at a temperature somewhat above ambient temperature,because in general cleaning is improved at elevated temperatures. Forelevated temperatures, in the case of shell and tube type geometries,and more particularly for small-dimensioned devices such ashemodialyzers, it is probably easier to maintain a large flow ratethrough the shell region as compared to the tube region. Thus, the flowthrough the shell region could be warmed in addition to or instead ofwarming the mixed-phase flow, to assist in warming up the entire deviceand maintaining it at temperature. The entire device could also bewarmed as well.

After the above cleaning sequences have been carried out, the cleanedsurfaces may also be rinsed or flushed to remove any traces of thecleaning agents which were added to form the liquid cleaning solution.When the liquid cleaning solution is water-based, this may be performedwith water or it may be carried out using a two-phase solution of waterand gas, either at the mixing ratio previously used, or at some othermixing ratio which is optimal for rinsing. Rinsing refers to amixed-phase flow containing pure liquid, and flushing refers toall-liquid flow. Lastly, the procedure may also comprise drying thepassageway using dry gas. With conventional liquid chemical disinfectionor sterilization procedures it is common that the next-to-last step is arinse with alcohol or an alcohol solution such as 70% alcohol in water,followed by drying with a dry air flow. This could easily be carried outwith the present method.

In the case of weak adhesion, mixed-phase flow containing only a gas anda pure liquid such as water or alcohol, may be sufficient to effect goodcleaning. However, important additional benefits can be obtained byadding a cleaning agent to the liquid It is known that surfactants canpenetrate the residue to be removed and diffuse at the interface betweenthe residue and the surface to be cleaned. This causes weakening of thebonding and adhesion forces at this interface, increasing the distancebetween the residue and the surface, which is commonly called the stericeffect, and in some cases, increasing their electrostatic repulsion.This action, when combined with the mechanical action of mixed-phaseflow, promotes faster and more efficient cleaning and removal ofresidues. The surfactant composition of the liquid cleaning mixture istherefore important, as are the pH and the oxidation potential of thecleaning liquid. Soluble inorganic compounds that have surface cleaningabilities can also be added. Surfactants typically have a molecularstructure which has a hydrophilic head and a hydrophobic tail. Thesurfactants used in the liquid phase can include a plurality ofsurfactants, including anionic, cationic, nonionic and amphoteric types.

Suitable anionic surfactants include fatty acid soaps covering a rangeof alkyl chain length up to about 18 carbon atoms and may be straight orbranched chain alkyl groups. These surfactants are normally used at a pHhigher than the dissociation constant of their corresponding carboxylicacid. Another class of anionic surfactants that has been found to beeffective with the present method is alkyl sulfates and sulfonates, suchas sodium dodecyl sulfate (SDS). Yet another useful anionic surfactantmay be based on alkylpolyoxyethylene sulfate. Another anionic surfactantthat can be used is an alkylbenzene sulfonate. Linear and branched chainalkylbenzene sulfates with one or more sulfonate groups have been foundto be useful. Suitable anionic surfactants also include alpha-olefinsulfonates, monoalkyl phosphates, acyl isothionates, acyl glutamates,N-acyl sarcosinates and alkenyl succinates and the like that have ananionic surface group and possess surface activity.

Suitable amphoteric surfactants include alkyldimethylamine oxides,alkylcarboxy betaines, alkylsulfobetaines, amide-amino acid typeamphoterics and others that may exhibit amphoteric and surface activity.Amphoteric substances have characteristics of both acid and alkaligroups.

Useful nonionic surfactants include polyoxyethylene alkyl ethers,polyethylene alkylphenyl ethers, polyethylene fatty acid esters,sorbitan fatty acid esters, polyethylene sorbitan fatty acid esters,sugar esters of fatty acids, alkyl polyglycosides, fatty aciddiethanolamides, fatty acid monoglycerides, alkylmonoglyceral ethers,fatty acid polypropyleneglycol esters and the like.

Cationic surfactants useful herein include alkyltrimethylammonium saltsand their phosphonium analogues, dialkyldimethyl ammonium salts,alkylammonium salts, alkylbenzyldimethylammonium salts, alkylpyridiniumsalts and the like which bear cationic functional groups and possesssome surface activity.

Polymeric dispersants are also useful herein. Although they do not havethe molecular structure of a typical surfactant, they have similareffects. These include formaldehyde condensates of naphthalenesulfonate, sodium acrylates or copolymers of other acrylic acids,copolymers of olefins and sodium maleate, lignin sulfonates,polyphosphates, silicates and polysilicates, carboxymethyl cellulose,cationic cellulose, cationic starches, polyvinyl alcohol, polyethyleneglycol, polyacrylamides and the like. These compositions are also usefulherein as surfactants. There are also detergent substances which are notstrictly surfactants. Examples include trisodium phosphate,sodium-carbonate and polymers. Such substances can also be used with thepresent invention.

Another factor is the degree of foaminess that is created by the use ofthe surfactant. As already described, some degree of foaminess isbelieved to be helpful for cleaning. However, excessive foaminessdecreases the velocity of the mixed phase flow and sometimes leads tonear stoppage of the flow. Therefore, either the surfactant(s) used inthe liquid cleaning solution must possess intrinsically low foamingproperties, or else an antifoaming or defoaming agent can be added tothe cleaning solution. Such agents are known and are commerciallyavailable.

Another important parameter in the cleaning liquid is its viscosity,since the liquid viscosity affects the mechanical action of the mixedflow cleaning method. In the case of aqueous solutions, the viscosity ofthe cleaning liquid can be adjusted upward if desired by adding watersoluble polymers, such as carboxymethyl cellulose, hydroxyethylcellulose, polyacrylic acid or any other viscosity increasing agents.

Chelating agents such as citrates, phosphates and ethylenediamine sodiumsalts and the like are useful in some applications for reasons includingwater softening, and to promote the removal of inorganic scales fromsome surfaces such as the surfaces of water pipes, heat exchangers,membranes and the like.

It is also possible to add a humectant into the formulation. A humectantis absorbed into the debris and in turn absorbs water, which helpsloosen the debris. Suitable humectants include glycerol, sorbitol,ethylene glycol and the like.

The optimum pH of the cleaning solution depends on the nature of thematerial to be removed. For removal of organic deposits, an alkalinesolution is preferred. PH adjusting additives can be used, as is knownin the art. For removal of inorganic deposits, such as scale, an acidicsolution is preferred.

An example of a useful non-surfactant aqueous solution is alcohol inwater. One particularly appropriate alcohol is ethanol, which is widelyused as a disinfectant but is not inherently toxic. The physicalproperties of alcohols, particularly ethanol, for surface tension andviscosity adjusting agents, are similar to those of water. Thus, anaqueous solution of alcohol will resemble water.

A biocide, a germicide or a disinfectant can be added to the cleaningsolution, such as gluteraldehyde, or peracetic acid. Peracetic acidexists only in equilibrium with some concentration of hydrogen peroxide.

An oxidizing agent may be added to the liquid cleaning solution to helpkill any bacteria which may not be physically removed by the mixed phaseflow treatment. Oxidizing agents can be selected from oxygen- orchlorine-based agents such as sodium hypochlorite or sources of thesame, and hydrogen peroxide or sources thereof, as well as otheroxidizing agents. It is possible to form hydrogen peroxide from hydrogenperoxide precursors, such as percarbonate or perborate, while the flowis flowing through the passageway. A catalyst can also be included tohelp the oxidizing action, as is known.

Ultrasound can also be used, either simultaneously with mixed phasecleaning, or at some other time. The ultrasonic vibration may help toloosen and dislodge biofilm, debris and contaminants, particularly inconjunction with the cleaning action of the mixed phase flow. Thismethod is particularly appropriate for cleaning hemodialyzers, when thecleaning liquid fills the dialysate side, because ultrasound travelswell through the dialysate side liquid to reach the fibers themselfes.The entire hemodialyzer can be immersed in a liquid bath which transmitsthe ultrasound, or by contacting ultrasonic transducers to the outsideof the hemodialyzer, or any other way known by one skilled in the art.

A cleaning solution of particular utility herein is an aqueous solutionincluding hydrogen peroxide. Since hydrogen peroxide decomposes to formfree oxygen, oxygen is available to oxidize organic matter and killmicroorganisms. Thus hydrogen peroxide cleaning with a mixed-phase flowis found to have better results in reducing bacterial count thancleaning with mixed-phase flow of pure water. Hydrogen peroxide is not asurfactant, but when hydrogen peroxide acts on biofilm, it chemicallyattacks the biofilm in such a way that it loosens the attachment of thebiofilm to the surface. The loosened biofilm can then be flushed out ofthe system being cleaned. Another advantage of hydrogen peroxide is thatits only other decomposition product besides oxygen is water, precludingany disposal problems.

Solid particles can also be added to the mixed phase cleaning solution.The particles added may be soluble or insoluble in water. Examples ofsuitable solid particles include water soluble sodium bicarbonate, andwater insoluble calcium carbonate. Solid particles may provide ascrubbing action in addition to the mixed phase flow. It may also beadvantageous for the solid particles to be a solid oxidizing agent.

An important advantage of this invention is that the time required toremove biofilm, debris and contaminants is relatively short,approximately several minutes. This is in contrast to liquid chemicaldisinfection which soak the passageway for durations of sometimes manyhours or days, when they still do not physically remove the structuralmatrix of the biofilm.

Reference is now made to FIGS. 2 through 8, which illustrate the presentinvention in greater detail.

The cleaning method of this invention can be applied to the geometry ofa simple round tube, such as dental unit water lines and water or fluidlines for other medical devices such as endoscopes, kidney dialysisequipment, or to more complicated geometries, such as tubes or conduitswhose cross-section is noncircular, e.g. elliptical, rectangular and thelike, or a closed curve. The tube or conduit can include within it someother internal component or components defined by boundaries which areits own closed curve or curves. This can, for example be an annulargeometry with an internal tube or object, as shown in FIG. 2.

FIG. 2 illustrates an outer tube 210, including therein an inner tube220. The inner tube 220 is axial, but this is optional. In general,either outer tube 210 or inner object 220 or both could instead have across section of some other shape, such as elliptical or rectangular.The inner tube 220 may be a fluid-carrying tube or carry othercomponents. The space 230 between the inner object 220 and the outertube 210 has an annular cross-section and has a substantial length withtwo ends, defining a passageway. This passageway 230 carries mixed-phaseflow during the cleaning process. This geometry is found in heatexchangers, catheters, biopsy devices, endoscopes and dental handpieces.The exterior of an endoscope may be cleaned by this method if theendoscope is enclosed in a temporary sheath, thereby defining an annularpassageway 230 between the exterior of the endoscope and the interior ofthe sheath.

FIGS. 3A and 3B show a cross sectional view of a biopsy device 300. InFIG. 3A the biopsy device 300 comprises a central wire 320 which issurrounded by a sheath 310. The sheath 310 may be made of a helicallycoiled wire having multiple turns 315. The central wire 320 is movedaxially relative to the sheath 310. At the other end is a device 350 forgrasping, cutting and retaining a piece of bodily tissue when thecentral wire 320 and the sheath 310 are moved relative to each other. Inorder for mixed-phase flow to be introduced for cleaning, it isconvenient to use access points already designed into the biopsy device,i.e., where wire 320 enters and leaves the sheath 310. This flow path isshown in FIG. 3A. If this is not practical and the coiled wire is bare,the coils may be temporarily stretched apart near one or both ends toprovide flow space. In a typical commercially available biopsy device,the coil or sheath 310 is uncoated and the coils are capable of beingstretched apart to provide access for the mixed-phase flow. In anothercommercially available biopsy device the coil or sheath 310 is coated,but at each end a suitable clearance exists so that flow can passthrough the device to perform cleaning. Cleaning of the outside surfaceof the biopsy device can also be accomplished using mixed-phase flow byencompassing the exterior of the biopsy device into a tube of slightlylarger diameter 380, as shown in FIG. 3B.

FIG. 4 illustrates a dental handpiece 410 for high-speed drills, whichtypically carries several fluid lines to and/from the drill 460. Insidethe handpiece 410 is an air path comprising an air supply line 420 whichbifurcates into a first branch 422 which is discharged as chip airtoward the drill 460 to blow away chips. The air supply line 420continues to a second branch 424 which leads to a turbine 430 and whichthen returns through return air path 440. Using the mixed-phase flowcleaning method, it is possible to simultaneously clean both branches422 and 424 of the air path 420. Separately located within handpiece 410is a water tubing 450 which discharges water to spray at the region ofthe drill 460. The water tubing can also be cleaned by the method of theinvention.

Several variations on handpiece design are known and can be cleaned bythe method of the invention. In some handpieces the chip air isdischarged coaxially around the water discharge, so as to break up thewater discharge into a spray; others have a completely separate fluidpath and connection for the chip air instead of having chip air branchoff from the turbine air supply. In another design, all of the fluidpassageways are located coaxially where the handpiece joins theutilities supply cord. This creates some annular flow geometries asdescribed earlier. In a more complex design, the return air from theturbine is made to flow into a space which is generally annular butwhich is subdivided at annular intervals. This can also be described asa number of passageways in parallel, with each passageway having anelongated cross-section. This irregular shape and cross-section alsorequires cleaning and can be cleaned using the present invention.

The method of the present invention is applicable to cleaningpassageways containing other bifurcations or divisions as well. A crosssection of a shell-and-tube-type heat exchanger is illustrated in FIG.5. Fluid enters through inlet port 505 and is divided in an inlet heater510 including a plurality of parallel, either circular or non-circularconduits or tubes 520. The other ends of the tubes 520 are connected toan outlet header 530 which leads to an outlet port 540. In FIG. 5 only12 tubes are shown, but any number can be present. Flow which enters theinlet header 510 must divide into many individual paths and then mustcome back together into one path at outlet port 540. This descriptionapplies to both the flow of fluid during normal operation and the flowof mixed-phase fluid during cleaning.

Opposed to the tubes 520 is a shell 542. This shell 542 is housing orenclosure which surrounds the tubes 520 and contains the fluid to whichthe exteriors of the tubes 520 are exposed. The shell side has two fluidport connections, a first connection port 550 near one end of the shell,and a second connection port 560 near the opposite end of the shell. Oneof these is a fluid inlet and the other is a fluid outlet as shown bythe arrows. Tube sheets 570 and 571 provide a structural connectionbetween the tubes 520 and the shell 540 and a seal which separates thefluid on the tube side from the fluid on the shell side. The geometryseen by the fluid inside the shell 542 is somewhat irregular. Betweenports 550 and 560, the flow is somewhat parallel to the interior objectswhich were described in FIG. 2. However, near the first and second fluidports 550 and 560, there are places where the internal objects separateout from the flow and the flow transitions to the inlet port 550 and theoutlet port 560 or vice versa. This also results in a type of dead-endpassageway which is a special case as far as cleaning is concerned.

Some heat exchangers are constructed with U-shaped tubes inside a shell,or with still other geometries, and some heat exchangers involve fins ofvarious geometries. The present invention is useful for cleaning any ofthem.

The preceding devices have solid surfaces. Devices which include poroussurfaces are discussed below.

Devices for filtration, reverse osmosis and hemodialysis use membranesto separate particles, substances or macromolecules from a liquid,typically water, by allowing the liquid to flow through the membraneswhile preventing particles of other substances or macromolecules fromflowing through the membrane, thereby separating them. The membrane hasa large surface area and is frequently tubular, but not necessarily ofcircular cross section. A liquid such as water flows under pressurealong a fluid passageway which is lined with or made entirely from aporous membrane material. Various membrane designs separate solids,bacteria, dissolved materials, viruses and the like from drinking water,wastewater, blood, food products and the like. Such filters can be usedfor the purification of brackish or salt water (desalination), and forthe recovery of potable water from wastewater.

In addition to exposed surfaces, e.g., surfaces directly exposed to themixed-phase flow during cleaning, the membrane has pore surfaces whichare the surfaces of narrow passageways through the membrane. This isillustrated in FIG. 6, which shows a cross-section of a permeablemembrane having the form of a tube. A membrane 600 has an exposedsurface 610 on the side which faces the mixed-phase flow, and severalpores 620 extending from the exposed surface 610 through the membrane600 to its opposite surface 622. The pores 620 may be simple holesresembling tubes on a small scale, or, more likely, they form athree-dimensional network 621. In FIG. 6 curved corners 624 are shownwhere the pores meets the exposed surface. Cleaning such permeablemembranes is more complex than cleaning solid surfaces because whateveris held back by the membrane can lodge either immediately at themembrane exposed surface 610 or within the membrane pores structure 620,which is more difficult to clean.

The method of the present invention can be used to clean both theexposed surface 610 and at least some of the pore 620. In order toremove solids from the membrane pores surface 610, it is necessary tothoroughly clean the membrane exposed surface 610, because if biofilm orother substances are not removed from the membrane exposed surface 610,they prevent particles and other contaminants from being removed fromwithin the membrane pore 620.

As an example of such a membrane device, a hemodialyzer filter usesmembranes to separate waste products from blood by allowing the wasteproducts to pass through the membrane but not the desirable componentsof blood. A hemodialyzer works on the basis of osmotic differences, butsome are microfilters, that is, a difference in chemical concentrationbetween the two sides of the permeable membrane, and does not have aslarge a pressure difference across the membrane as does reverse osmosisand ultrafiltration. Typically the geometry in a hemodialyzer comprisesa plurality of hollow fibers which can number up to about 15,000. Theblood from the patient is on the inside of the hollow fibers and insidethe headers at each end of the dialyzer. Thus the primary surfaces whichmust be cleaned and disinfected in order for a dialyzer to be re-usedare the interior of the hollow fibers and the headers. The exterior ofthe hollow fibers are exposed to the dialysate, a fluid which absorbsand carries away waste substances from the patient's blood. Ahemodialyzer may be used repeatedly. The pores of its membranes can clogwith biological material, and the cross section of individual hollowfibers can also become blocked, leading to diminished performance.

The primary differences between a heat exchanger and a hemodialyzer arethat the walls of the tubes are porous, and the tubes have differentdimensions and proportions. As shown in FIG. 5, a hemodialyzer comprisesa plurality of permeable narrow, hollow fibers (tubes) 520, all of whichare connected to an inlet 510 at one end and to an outlet 530 at theother end. A housing 540 encompasses the tubes 510. The diasylate fluidenters the housing 540 at inlet 550 and exits through outlet 560. Byapplying the highest pressure to the ports 550 and 560, backflushing iscarried out.

During the mixed-phase cleaning procedure, the fluid on the dialysateside can be, but does not have to be, circulated continuously. Oneuseful function of the liquid on the dialysate side is that it can alsobe at an elevated temperature so as to help warm up the entirehemodialyzer and maintain it at temperature. Other means of heating thehemodialyzer are also possible, including convection, infraredradiation, preheating and the like. Of course, the mixed-phase flowinside hollow fibers 720 can itself be warm. It is believed that optimumcleaning will occur when the surfaces being cleaned are at a temperaturewhich is higher than room temperature, but not so high as to causeirreversible chemical reactions in the deposited biological material,which might make it more difficult to remove.

In the case of a hemodialyzer, the permeability of the membrane is suchthat the quantity of water or liquid which seeps through the membraneduring the cleaning process, if the dialysate side is pressurized to ahigher pressure than the interior of the hollow fiber, may be sufficientto create the two-phase flow situation inside the hollow fiber. In thismanner it may be possible to provide only flow of dry gas into thepassageway. This gas flow would then become two-phase as a result ofmixing with the permeated liquid. In this case the two-phase flow wouldhave an increasing liquid content as it progresses from the inlet to theoutlet of the passageway, due to additional liquid seeping in along thepassageway. In itself, this variability of liquid fraction is not anintended feature of this mode of operation, but it may be convenient.

Geometries for filtration applications such as microfiltration,ultrafiltration and reverse osmosis, are similar to the shell and tubeheat exchanger and the hemodialyzer. The one difference with respect tothe geometries of a shell-and-tube heat exchanger or a hemodialyzer isthat typically only three connections are actually used. On the sidecontaining purified fluid, usually only one connection needs to be usedbecause there is only outflow. The outflowing purified liquid is termedpermeate.

In the tubular filter of FIG. 7, the contaminated liquid flow path isone undivided flow path extending from the inlet 710 to the outlet 730.However, that flow path 720 may zig-zag back and forth a number oftimes, by means of return bends. Clean filtered liquid is collectedinside the housing and can be withdrawn through either or both of theinlet and outlet ports 750, 760 through the boundary of the housing 740.The surface to be cleaned is the interior of the passageway from theinlet to the outlet.

There is another filter geometry which is used in filtration,ultrafiltration and reverse osmosis, called a spiral wound membranefilter as shown in FIG. 8. In this case, two rectangular membrane sheets810, 812 are separated by a porous structural layer 820 and are sealedto each other along three edges 830, 832 and 834, forming a pocket ormembrane assembly 870. A tube section 880 is manufactured with smallholes 882 in a line along most of its length. Optionally, one end of thetube 880 may be closed. The membrane assembly 870 is attached in aleaktight manner to tube 880 such that the small holes 882 are exposedto the interior of the pocket formed by the two membrane sheets 810,812. The membrane assembly 870 is then wound around the tube 880 in aspiral fashion, with a spacer 890 separating layers of the winding.Although FIG. 8 shows only one membrane assembly 870, it is possible fora filter to be constructed using more than one such membrane assembly,up to as many as twelve. Preferably, the junctions of the variousmembrane assemblies 870 to tube 880 are uniformly spaced about thecircumference of the tube 880. The spacer 890 is typically a coarse meshhaving the same overall dimensions as the membrane sheets 810, 812 andit may contain channels. The spacer 890 provides a flow path forcontaminated liquid, allowing the contaminated liquid to contact almostthe entire surface of the membrane sheets 810, 812. This entire rolledassembly is then placed inside a housing 840. Contaminated liquid issupplied to the outside surface of the membrane assembly 870, inside thehousing 840. There are two ports 850 and 860 which connect to thehousing 840 for the purpose of supplying and removing a flow ofcontaminated liquid.

Permeate flows through the membrane into the porous structural layer 820which separates membrane sheets 810 and 812. The permeate moves throughthe structural layer 820 in a spiral path until it reaches the centraltube 880 which collects the filtered liquid. In this example,contaminated liquid is supplied on the outside of the membrane assembly870, between the membrane and the housing 840. Purified liquid iswithdrawn through the central tube 880. Contaminants accumulate on allsurfaces of the membranes 810 and 812 which are exposed to thecontaminated liquid. The exposed membrane surfaces must be cleanedperiodically to ensure proper operation of the filter assembly. It isdifficult to clean these surfaces because they are inaccessible andrestrict flow velocities. However, the method of the present inventionis well suited for cleaning such filters.

Another geometry which can be cleaned by the method of the invention isone in which the flowpath divides into many parallel paths, as in ahoneycomb, where there is flow of the same fluid on both sides of apassageway boundary. Such a geometry may be made of ceramic, and can becleaned by the present method.

The present invention will be further described in the followingexamples. However, the invention is not to be limited to the detailsdescribed therein. In the examples, water is distilled water.

EXAMPLE 1

This example illustrates cleaning of a dental handpiece having a complexinternal geometry. The flow path of fluid through the handpiece is showngenerally in FIG. 4, except that the return path is divided into anumber of angularly spaced subdivisions. The internal diameter of thetubing varied from {fraction (1/32)} to {fraction (1/16)} inch. Thetubing was thoroughly cleaned between experiments.

The handpiece was inoculated with an initial bacterial load of 4×10⁶Bacillus steariothermopholia spores (ATCC 7953) distributed among fourchosen sites experimentally known to be the worst sites for cleaning.

The handpieces were then subjected to various cleaning techniques as setforth below. Then the cleaned handpieces were placed in sterile growthmedium, and incubated for two days. The bacterial growth was thenmeasured.

Part A. Surfactant Only.

The cleaning solution was a surfactant available as CPC-718 from VWRScientific, which is a mixture of amphoteric and anionic surfactants.The solution was diluted to a 10% by volume solution with water. It hada pH of 10.5 at a temperature of 55° C. Air under pressure of 80 psigwas passed into the handpiece for 15 seconds, a two-phase flow of airand solution passed through for five minutes, followed by a two-phaserinse with water for one minute. No bacterial growth was noted after twodays.

Part B. Peroxide, No Surfactant.

The method of Part A was followed except that 3% of hydrogen peroxideand a mixture of transition metal organic complexes that improved theefficiency of radical generation in oxidation reactions was used as thecleaning solution. This solution had a pH of 10.4 and a temperature of45° C. Air at a pressure of 80 psig was passed through the handpiece for15 seconds, a two-phase mixture of air and the above solution for 3minutes, followed by a two-phase water rinse. No bacterial growth wasnoted after two days.

Part C.

Dental handpieces manufactured by Star Dental, containing a complicatedinternal geometry, were used for this test. The cleaning reported herewas for the flow path defined by the drive air plus chip air plus exitair circuit, similar in principle to the air flow path illustrated inFIG. 4. For the incoming part of the flow path, the geometry was asimple tube leading into the turbine and the chip air discharge, and forthe exiting part of the flow path the geometry was the return path ofair from the turbine. There is, however, a slight difference from theillustration in FIG. 4, in that the exiting flow path 440 was an annulusdivided into a number of angularly spaced subdivisions.

EXAMPLE 2

The method of Example 1 was repeated but cleaning the internal waterline channel of the dental handpiece, which was a simple tubularpassageway. Similar results were obtained.

EXAMPLE 3

A biopsy device containing a cable inside a polymer-coated sheath,having an outside diameter of 0.084 inch, was used in this example. Theaccess for fluid flow to clean the region between the cable and thesheath was at each end of the sheath where the cable entered or exitedfrom the sheath using existing clearances. Cleaning between the sheathand the cable was tested by connecting the flow source to an existingthreaded connection at the operator's end of the biopsy device. The flowthen exited at the other end of the biopsy device where the tissueremoval blades are located.

For cleaning the exterior of the biopsy device, the entire length of thedevice was inserted into a clear plastic tube which served as apassageway to direct flow along the outside of the device. The insidediameter of the clear plastic tube was about 50% larger than the outsidediameter of the device.

Air was supplied at a pressure of 50 psi, and a gas/liquid flow rateratio of several hundred to one, using sodium dodecyl sulfate surfactantin water. In both cases, the flow characteristics produced provided goodcleaning, as determined by visual observation.

EXAMPLE 4

An ultrafiltration filter having about 300 hollow fibers, each having aninner diameter of 1.1 mm, was cleaned using the mixed phase cleaningmethod of the invention. The filter cartridge was about 7 inches long.The membrane material was polysulfone having a molecular weight maximumof about 100,000. The cartridge was designed to operate with permeaterates of 202 ml/min at 25 psi operating pressure. The interior of thehollow fibers were fouled with a mixture of Bovine Serum Albumin,calcium chloride and magnesium chloride.

Fouling was continued until the permeate rate was reduced to half of itsinitial flux. The fibers were cleaned using an aqueous solution ofamphoteric surfactants at an air pressure of 15 psig for two minutes.The flux of the membrane was brought back to its initial value.

The above procedure was repeated except that the membrane was cleanedusing a single phase flow of a solution of nonionic surfactant alone for30 minutes. The permeate recovered to a rate of 134 ml/min or only 55%of its initial value.

The procedure was repeated except that the membrane was cleaned using asingle phase flow of aqueous solution containing 0.25% of sodium dodecylsulfate for 60 minutes. However, the permeate plateaued at a lower ratethan its initial value.

The Reynolds number of the flow through the interior of the fibers canbe calculated based on the known flow rate and cross-sectional area ofair flow, the fiber diameter and the air viscosity. The calculatedReynolds number is in the upper hundred, which is within the laminarrange. It is believed that cleaning action is best if the gas flow isturbulent, but this shows that even at the upper end of the laminarrange, effective cleaning of hollow fiber ultrafiltration cartridges canbe achieved.

EXAMPLE 5

Part A

A contaminated liquid was applied to the outside of hollow fibers of thesame type of filter used in Example 4. The contaminating liquid was amixture of gelatin and a dye. The cleaning solution contained sodiumcarbonate together with a surfactant “Tergitol”, a trade name of UnionCarbide Corporation. The air/liquid ratio was relatively wet at about100:1 and the air pressure was 30 psig. The hollow fibers are ratherflexible and, when wet, they can clump together which hinders cleaning.Thus the flow was pulsed and run for a somewhat longer period of time.Good cleaning was achieved.

Part B

The same geometry, i.e., cleaning of the outsides of a group of hollowfibers, can appear when there is no real housing at all about thefibers, but rather the fibers simply traverse open space between twoheaders that have some structural connection to each other. Duringnormal use, the group of fibers is immersed in a body of possiblycontaminated water, with clean liquid being withdrawn by suction fromthe insides of the fibers. Cleaning can be performed by directingmixed-phase flow at the exteriors of the hollow fibers. In such case ithas also been found helpful to apply ultrasound simultaneously with themixed-phase flow.

EXAMPLE 6

A rather large tubular filter, illustrated in FIG. 7, having a length ofabout 6 feet including 8 individual tubes connected in series so theoverall flow length inside the tubes was 48 feet, having a flow pathwith a total of seven return bends of 180 degrees each, available fromthe Zenon Environmental Co. of Burlington, Ontario, Calif., was used asan ultrafilter during a wastewater treatment operation. The tubularmembrane was Zenon MT-100 having a molecular weight maximum of about100,000. The inside diameter of the tube was about 0.8 inch.

Waste water was supplied to the inside of this tube and clean water wasextracted from the outside. During cleaning, the air supply pressureranged from 40-80 psig. The flow rate of air was 120 standard cubic feetper minute. The velocity of the air was calculated to range from about40 m/s near the inlet to about 175 m/s near the outlet. The Reynoldsnumber of flow of air in these tubes was 225,000. The flow regime wasfilm flow or light foam. The structure of this filter was such that itwas not permissible to significantly backflush.

Part A

The filter was treated by a controlled synthetic wastewater until itsflux decreased to 39% of its as-manufactured value. The filter was thencleaned by the two-phase cleaning method using several steps, includingboth acidic and alkaline cleaning liquids. The surfactant concentrationof sodium dodecyl sulfate was 1%. Using an air:liquid ratio of 200:1,and an alkaline surfactant for 3 minutes, the flux recovered to 64% ofits initial value. Applying the two-phase flow for another 2 minutesimproved the flux to 81% of its initial value. Additional cleaning usinghydrogen peroxide and a transition metal catalysyt did not improve theflux further. Only a slight improvement in the flux values were realizedwhen the two-phase flow was reversed.

These results show that a total of five minutes cleaning of a tubularfilter using two-phase flow is sufficient to restore the flux values andcompares favorably with conventional cleaning requiring a much longerperiod of time. Repetition of the above cleaning gave similar results.

This experiment also illustrates the re-formation of the mixed-phaseflow condition after a sharp change of direction. At each return bend itcan be expected that there might be some disturbance of the mixed-phaseflow condition, such as coalescence of droplets, but the successfulcleaning results show that there is rapid re-formation of themixed-phase flow condition after a flow irregularity, such as a bend.

Part B

In another experiment, the same type of filter was fouled by acontrolled wastewater to the point where its flux level dropped to 35%of its initial value. Cleaning was performed and then stopped, while theflux was measured briefly using the controlled wastewater. Cleaning wasresumed, and this was repeated several times until it became apparentthat no further improvement was obtained. After three intervals of suchcleaning, all at the same mixed-phase flow conditions, the flux levelreached a plateau of about 74% of the baseline and no furtherimprovement was obtained. To obtain further improvement, soaking wasinitiated because both the surface and pore structure of the tubularmembrane had become fouled. For a period of time, the passageway wasfilled with foam which was stationary, and pressure continued to beapplied in the same direction as normal operation of the filter. Thisallows the cleaning solution to reach deeper into the pores. This holdand soak cycle lasted 2 minutes, and was followed by the application oftwo-phase flow for 15 seconds to remove any newly-dislodged residue. Thesoaking brought a further improvement up to 95% of the baseline value.

Part C

Three additional filters were cleaned. Two of them had been fouled bynormal use until the flux was about 40% of its initial value, and onehad been fouled by normal use until the flux was only 4% of its initialvalue. All three were cleaned with a solution of an amphotericsurfactant and potassium hydroxide having a pH of 12.8. The cleaningcycle included several minutes each of two-phase flow and a holdingperiod, with internal pressure under static conditions. A lightbackflushing was then performed using the liquid cleaning solutionpressurized on the permeate side to several psi.

For the most heavily fouled filter, a further treatment was performedusing an acidic two-phase flow cleaning for three minutes, followed byan alkaline two-phase flow cleaning for three minutes. The first twofilters were restored essentially to 100% of their initial flux, and thelast was restored to about 95% of its initial specified flux.

EXAMPLE 7

A typical hemodialyzer, Model 80B manufactured by the Fresenius Co. ofBad Homburg, Germany, was used. The internal diameter of a hollow fiberis 0.2 mm and the length to diameter ratio of each fiber is 1100. The15,000 parallel hollow fibers were made of polysulfone. Experiments wereperformed on hemodialyzers which had been used for human patients, withreprocessing by conventional techniques after each use, until theyfailed the condition for re-use which is based on the total internalvolume of the hemodialyzer (Total Cell Volume, or TCV). Thehemodialyzers were then re-processed using the mixed-phase cleaningmethod. The mixing ratio was about 200:1 of air to liquid, and thecleaning solutions included surfactants and oxidants. The sourcepressure of the gas was 55 psig, and the flow rate was determined by howmuch flow of the mixed-phase mixture could pass through the 0.156 inchdiameter inlet port and outlet port, the end caps of which were left on.The duration of treatments with mixed-phase flow was about 10 minutes.

The result was efficient removal of the proteins, blood cells andcomponents from the lumens of the hollow fibers, as shown by SEMexamination and actual TCV measurements. Improvement was visuallyobserved in the condition of the end cap or header regions of thehemodialyzers after cleaning. After conventional cleaning, traces ofblood were frequently visible in the header regions. After cleaning withtwo-phase flow, no such traces of blood remained.

The Reynolds number of the flow in the hollow fibers can be calculatedbased on the known flow rate and cross sectional area of air flow, thefiber diameter and the air viscosity. The calculated Reynolds number isabout 200, within the laminar range. It is believed that cleaning actionis best if the gas flow is turbulent, but even within the laminar range,effective cleaning of hemodialyzer cartridges. It may be that eventhough the attainable gas velocities are rather low for achievingsignificant droplet impact forces, the process of ripping off dropletsfrom the liquid layer creates forces on the biological materials whichhave been deposited in the pore structure, or on the exposed surface,thereby assisting in their removal.

EXAMPLE 8

A hemodialyzer was cleaned by introducing an aqueous cleaning liquidincluding sodium bicarbonate into the dialysate side, At the same time,a solution including acetic acid was introduced in the form of mixedphase flow. When the two liquids came together near the membranesurface, the reacted to liberate carbon dioxide in the form of bubbles.Good cleaning was observed visually.

EXAMPLE 9

A hemodialyzer was cleaned by filling the dialysate side with apressurized solut8ion of carbonated water. The pressure drop that thecarbonated water experienced flowing across the membrane from thedialysate side to the lumen side caused bubbles of carbon dioxide tocome out of solution. Good cleaning action was visually observed.

EXAMPLE 10

A hemodialyzer was cleaned with a cleaning solution including sodiumhypochlorite, NaOCl. A two-phase cleaning solution including 0.25% ofNaOCl resulted in good cleaning in ten minutes. The cleaning solutionwas pumped into the dialysate side and dry air was supplied to theinterior of the hollow fibers, producing backflushing of liquid throughthe pores and two-phase gas-liquid flow inside the hollow fibers. Inthis case the cleaning solution as prepared for use contained nosurfactant, and no sudsing could be generated when shaken.

However, when the cleaning liquid exited the hemodialyzer and wascollected, substantial foaming was found in the collection vessel. Thusit is believed some chemical reaction occurred between the NaOCl and theorganic materials deposited in the hemodialyzer pores that resulted inthe creation of soap-like substances (saponification) which caused thefoaminess in the collection vessel. Furthermore, it is believed thatthose soap-like substances may have further aided in the solubilizationand removal of other protein substances from the pores of the membrane.It is also believed that the alkalinity of the NaOCl solution may alsobe of value in cleaning. The hemodialyser total cell volume wasessentially restored to its initial value.

After thorough rinsing or flushing, the cleaning step is followed by adisinfection step using a disinfectant/sterilant, such as peraceticacid-hydrogen peroxide mixtures. The cleaning solution can be warmed upto about 130° F. which is less than the temperature which would denatureprotein. Preferably, it is warmed only just before it is supplied to thehemodialyzer. Some pulsing of the liquid flow which occurred due to theoperating characteristics of the pump, may also be advantageous.Pulsation and refersal of the gas flow are also advantageous.

Although the above example describes the possible interaction of NaOClwith organic matter to produce surfactant-like substances or effects,the addition of a known surfactant to the cleaning liquid may also bedesirable. One suitable surfactant is Triton-X-100, which gives goodperformance. This nonionic detergent is often used in biochemicalapplications to solubilize proteins without denaturing them.

Another surfactant with similar properties is Cremophor EL, manufacturedby BASF Corporation, an ethoxylated castor oil, and other members ofthat family. This product is already used for parenteral drug deliveryin much larger quantities than a hemodialyzer patient could be exposedto. Chromophor EL is used for emulsifying and delivering the anti-cancerdrug paclitaxel. A suitable concentration of either of these surfactantsin the cleaning liquid is 200 ppm.

The cleaning solution containing NaOCl, either with or without asurfactant, is titrated with NaOH to a pH of 11.3.

During this cleaning procedure, clotted blood fibers several inches longcould be seen exiting from the hollow fibers of the hemodialyzer, alongwith the mixed-phase flow. Polysulfone dialyzers in particular havelimitations on the combination of concentration and time they can beexposed to NaOCl; however, a concentration of 0.225% NaOCl for about 10minutes when warmed to 130° F. achieved good cleaning. Pulsation oron/off flow every few seconds and occasional reversal of the air flowdirection through the hollow fibers were also employed. The TCV wasrestored to their initial values.

EXAMPLE 11

A spiral wound reverse osmosis filter manufactured by FilmTec Corp, asubsidiary of Dow Chemical Co., Model Number TW30-1812-50 was employedin this example. It is 10.5 inches in the axial direction and includesabout 14 turns of wrapped membrane with a pore size which is appropriateto pass water molecules, but not large molecules. Purified water(permeate) is extracted through the central tube, while contaminatedfluid accesses the filter through two ports, one at each end of thefilter, one used as an inlet and the other as an outlet for concentratedcontaminated water. Flux measurements were taken at differentialpressures of 30, 50 and 70 psi. When the filter was new, the flux ofpure water through the membrane was 38.6 mL/min at 30 psig, 86.4 mL/minat 50 psig and 133 mL/min at 70 psig. In all cases a flow rate of about2300 to 2800 mL/min was maintained on the upstream side of the membrane,which was always at least 17 times as large as the flux of filteredwater.

The membrane was intentionally treated with a synthetic mixturecomprising Bovine Serum Albumin (BSA), NaCl and a suspended solid whichincluded dried milk, soap, gelatin and starch. This mixture containscomponents which represent each of the three major mechanisms of foulingof reverse osmosis membranes, which are inorganic scaling, silting andbiofouling. This mixture was pumped through the high pressure side fortwo hours at a pressure of 60 psig. This caused the membrane flux to bereduced to 13.2 mL/min at 30 psi, 48.8 mL/min at 50 psig, and 79.4mL./min at 70 psig. Although the results differ somewhat from onepressure to another, most of these fluxes and their average are reducedto the range of 50-60% of the respective baseline flux values.

Several conventional cleaning sequences were performed involving onlyliquid phase (water and additives) being pumped through the contaminatedliquid side of the filter.

The filter was cleaned with a solution of 0.5% of nonionic surfactant at50 psi for 25 minutes. The flux recovered somewhat, to 26 mL/min at 30psig, 55 mL/min at 50 psig and 96.3 mL/min at 70 psig, which is about68% of their initial values.

Repeating the procedure using an anionic surfactant, 0.2% sodium dodecylsulfate at 50 psi for 25 minutes, the fluxes were 19.2 mL/min at 30 psi,53.4 m:/min at 50 psi and 89.8 mL/min at 70 psi, which showed noadditional improvement.

Cleaning was continued with an acid cleaning solution of phosphoric andcitric acids and a nonionic surfactant, but again there was noadditional improvement.

Cleaning was then continued with a solution of NaOH and amphoteric andnonionic surfactants for 25 minutes, but the flux remained at about ⅔ ofthe initial values.

Cleaning was then performed for 3 minutes using a mixed-phase mixture ofthe invention. The liquid was a mild alkaline solution (pH 10.5) ofwater, EDTA and amphoteric, anionic and nonionic surfactants togetherwith air under pressure of 65 psi, entering one and exiting another ofthe contaminated water ports. Some improvement was noted.

The mixed-phase cleaning was repeated with a higher flux of air, the airvelocity being about 30-40 m/s. After 3 minutes, the filter fluxreturned to its original value. This is a significant improvement overconventional cleaning methods.

EXAMPLE 12

Clear plastic tubing having an inside diameter of about 2 mm in whichbiofilm had been grown was cleaned using a solution of hydrogen peroxidein water and a gas at a supply pressure of 60 psig. Complete removal ofbiofilm was obtained.

In contrast, a mixed phase mixture at a pressure of 60 psi was passedinto the tubing for 3 minutes. The liquid was a solution containing 0.3%of Dowfax 9380 of Dow Chemical Co., a nonionic surfactant, 0.3% of F127nonionic surfactant, 0.3% of Tween 20 nonionic surfactant and 1% ofsodium carbonate in water. This mixture foamed so that little flowthrough the tubing occurred, and no cleaning was obtained.

Another solution of 0.2% of hydroxypropylcellulose in water was used.However, the viscosity of this solution is about 500 cp, 500 timesgreater than water, inhibiting the formation of droplets. Thus nocleaning was obtained.

Water alone was used to form a mixed-phase flow. In this case, becausewater has a high surface tension, it did not break up into smalldroplets which could follow the gas flow. Thus cleaning resulted in onlya slight decrease in bacterial count. However, cleaning with water alonemay be effective, such as when lightly adherent debris is to be removedfrom porous membrane surfaces.

A fluorosurfactant, Zonyl FSP made by DuPont Performance Chemicals inwater was also tried. This solution had a surface tension of 25 to 40dyne/cm, smaller than the usual detergent solutions. Cleaning was poorbecause at this low surface tension, droplets formed were too small tointeract with the tubing walls.

Thus the mixed-phase cleaning method of the invention is applicable tosolid passageway boundaries of any type, including plastics, metals,ceramics and the like. The method includes regimes of droplets dispersedin gas (froth, foam) and film flow which resembles a multiplicity offilms such as soap bubbles. The exact boundaries of parameter space forgood cleaning are difficult to define, because of the empirical natureof multi-phase fluid mechanics and because the requirements vary withthe amount of cleaning desired and the time available. Generally, thegas flow rate when liquid is added is at least 40% of the gas flow ratewhen no liquid is added. In general a supply air pressure of 60-100 psiis useful, but for some purposes supply pressures as low as about 15psig can be used, attainable with blowers rather than compressors.

It will be apparent that various cleaning solutions, temperatures,pulsation, soaking, sequential passage of solutions, with or without apressure difference as across a membrane either to force cleaningsolution into the pores or in reverse direction to force contaminantsout of the pores, can be used. Solid particles, soluble or insoluble,can also be added to the liquid. A final rinse with water can be used,or an alcohol-water rinse to promote drying. The scope of the inventionis not to be limited to the disclosure, but only by the scope of theappended claims.

1. A method for cleaning a pipeline comprising: (a) forming a mixture ofgas and liquid in the pipeline wherein at least a portion of the liquidis provided in the form of droplets; and (b) passing the mixture of gasand liquid through the pipeline at a flow rate and at a volumetric ratioof gas to liquid sufficient to provide a local shear stress at theinside of the pipeline of at least about 53 Pa and to provide thedroplets throughout the length of the pipeline.
 2. A method according toclaim 1, wherein the volumetric ratio of the gas to the liquid is atleast about 50:1 when measured at 1 atmosphere and 0° C.
 3. A methodaccording to claim 1, wherein the volumetric ratio of the gas to theliquid is less than about 6,000:1 when measured at 1 atmosphere and 0°C.
 4. A method according to claim 1, wherein the mixture of gas andliquid is provided within the pipeline at a velocity of at least about10 m/s.
 5. A method according to claim 1, wherein the mixture of gas andliquid is provided within the pipeline at a velocity of at less thanabout 100 m/s.
 6. A method according to claim 1, wherein the mixturecomprises a cleaning agent comprising at least one of a surfactant, anoxidizing agent, an alcohol, and a non-surfactant detergent.
 7. A methodaccording to claim 6, wherein the cleaning agent comprises an anionicsurfactant.
 8. A method according to claim 7, wherein the anionicsurfactant comprises at least one of fatty acid soaps having an alkylchain length of up to about 18 carbon atoms, alkyl sulfates, alkylsulfonates, and mixtures thereof.
 9. A method according to claim 7,wherein the anionic surfactant comprises at least one of sodium dodecylsulfate, alkyl polyoxyethylene sulfate, alkyl benzene sulfonate,alpha-olefin sulfonates, monoalkyl phosphates, acyl iosthionates, acylglutamates, N-acyl sarcosinates, alkenyl succinates, and mixturesthereof.
 10. A method according to claim 6, wherein the cleaning agentcomprises an amphoteric surfactant comprising at least one of alkyldimethyl amine oxides, alkyl carboxy betaines, alkyl sulfobetaines,amide-amino acid type amphoterics, and mixtures thereof.
 11. A methodaccording to claim 6, wherein the cleaning agent comprises a nonionicsurfactant comprising at least one of polyoxyethylene alkyl ethers,polyethylene alkyl phenyl ethers, polyethylene fatty acid esters,sorbitan fatty acid esthers, polyethylene sorbitan fatty acid esters,sugar esters of fatty acids, alkyl polyglycosides, fatty aciddiethanolamides, fatty acid monoglycerides, alkyl monoglycerol ethers,fatty acid polypropolene glycol esters, and mixtures thereof.
 12. Amethod according to claim 6, wherein the cleaning agent comprises acationic surfactant comprising at least one of ammonium salts,phosphonium salts, pyridinium salts, and mixtures thereof.
 13. A methodaccording to claim 6, wherein the mixture comprises a dispersant.
 14. Amethod according to claim 6, wherein the mixture comprises anantifoaming agent.
 15. A method according to claim 6, wherein themixture comprises a chelating agent.
 16. A method for cleaning amembrane, the method comprising: (a) applying a mixture of gas andliquid to a membrane in a housing, the mixture comprising the gas andthe liquid phase at a volumetric ratio of at least about 50:1 whenmeasured at 1 atmosphere and 0° C., and wherein at least a portion ofthe liquid is provided in the form of droplets and the liquid comprisesat least one cleaning agent.
 17. A method according to claim 16, furthercomprising: (a) rinsing the membrane with water.
 18. A method accordingto claim 16, wherein the volumetric ratio of the gas phase to the liquidphase is less than about 6,000:1 when measured at 1 atmosphere and 0° C.19. A method according to claim 16, wherein the membrane comprises atleast one of ultrafiltration membrane and a reserve osmosis membrane.20. A method according to claim 16, wherein the mixture is provided at avelocity of at least about 10 m/s.
 21. A method according to claim 16,wherein the mixture is provided at a velocity of less than about 100m/s.
 22. A method according to claim 16, further comprising: (a) soakingthe membrane with the liquid phase.
 23. A method according to claim 16,wherein the mixture is provided at a temperature above ambienttemperature.
 24. A method according to claim 16, wherein the cleaningagent comprises at least one of a surfactant, an oxidizing agent, analcohol and a non-surfactant detergent.
 25. A method according to claim16, wherein the cleaning agent comprises an anionic surfactant.
 26. Amethod according to claim 25, wherein the anionic surfactant comprisesat least one of fatty acid soaps having an alkyl chain length of up toabout 18 carbon atoms, alkyl sulfates, alkyl sulfonates, and mixturesthereof.
 27. A method according to claim 25, wherein the anionicsurfactant comprises at least one of sodium dodecyl sulfate, alkylpolyoxyethylene sulfate, alkyl benzene sulfonate, alpha-olefinsulfonates, monoalkyl phosphates, acyl iosthionates, acyl glutamates,N-acyl sarcosinates, alkenyl succinates, and mixtures thereof.
 28. Amethod according to claim 16, wherein the cleaning agent comprises anamphoteric surfactant comprising at least one of alkyl dimethyl amineoxides, alkyl carboxy betaines, alkyl sulfobetaines, amide-amino acidtype amphoterics, and mixtures thereof.
 29. A method according to claim16, wherein the cleaning agent comprises a nonionic surfactantcomprising at least one of polyoxyethylene alkyl ethers, polyethylenealkyl phenyl ethers, polyethylene fatty acid esters, sorbitan fatty acidesthers, polyethylene sorbitan fatty acid esters, sugar esters of fattyacids, alkyl polyglycosides, fatty acid diethanolamides, fatty acidmonoglycerides, alkyl monoglycerol ethers, fatty acid polypropoleneglycol esters, and mixtures thereof.
 30. A method according to claim 16,wherein the cleaning agent comprises a cationic surfactant comprising atleast one of ammonium salts, phosphonium salts, pyridinium salts, andmixtures thereof.
 31. A method according to claim 16, wherein themixture comprises a dispersant.
 32. A method according to claim 16,wherein the mixture comprises an antifoaming agent.
 33. A methodaccording to claim 16, wherein the mixture comprises a chelating agent.34. A method for cleaning a heat exchanger, the method comprising: (a)applying a mixture of gas and liquid to a tube side of a shell-and-tubeheat exchanger, the mixture comprising the gas and the liquid at avolumetric ratio of least about 50:1 when measured at 1 atmosphere and0° C., and wherein at least a portion of the liquid is provided in theform of droplets and the liquid comprises at least one cleaning agent.35. A method according to claim 34, wherein the volumetric ratio of thegas phase to the liquid phase is less than about 6,000:1 when measuredat 1 atmosphere and 0° C.
 36. A method according to claim 34, whereinthe mixture is provided at a velocity of at least about 10 m/s.
 37. Amethod according to claim 34, wherein the mixture is provided at avelocity of less than about 100 m/s.
 38. A method according to claim 34,wherein the mixture is provided at a temperature above ambienttemperature.
 39. A method according to claim 34, wherein the cleaningagent comprises at least one of a surfactant, an oxidizing agent, analcohol and a non-surfactant detergent.
 40. A method according to claim34, wherein the cleaning agent comprises an anionic surfactant.
 41. Amethod according to claim 40, wherein the anionic surfactant comprisesat least one of fatty acid soaps having an alkyl chain length of up toabout 18 carbon atoms, alkyl sulfates, alkyl sulfonates, and mixturesthereof.
 42. A method according to claim 40, wherein the anionicsurfactant comprises at least one of sodium dodecyl sulfate, alkylpolyoxyethylene sulfate, alkyl benzene sulfonate, alpha-olefinsulfonates, monoalkyl phosphates, acyl iosthionates, acyl glutamates,N-acyl sarcosinates, alkenyl succinates, and mixtures thereof.
 43. Amethod according to claim 34, wherein the cleaning agent comprises anamphoteric surfactant comprising at least one of alkyl dimethyl amineoxides, alkyl carboxy betaines, alkyl sulfobetaines, amide-amino acidtype amphoterics, and mixtures thereof.
 44. A method according to claim34, wherein the cleaning agent comprises a nonionic surfactantcomprising at least one of polyoxyethylene alkyl ethers, polyethylenealkyl phenyl ethers, polyethylene fatty acid esters, sorbitan fatty acidesthers, polyethylene sorbitan fatty acid esters, sugar esters of fattyacids, alkyl polyglycosides, fatty acid diethanolamides, fatty acidmonoglycerides, alkyl monoglycerol ethers, fatty acid polypropoleneglycol esters, and mixtures thereof.
 45. A method according to claim 34,wherein the cleaning agent comprises a cationic surfactant comprising atleast one of ammonium salts, phosphonium salts, pyridinium salts, andmixtures thereof.
 46. A method according to claim 34, wherein themixture comprises a dispersant.
 47. A method according to claim 34,wherein the mixture comprises an antifoaming agent.
 48. A methodaccording to claim 34, wherein the mixture comprises a chelating agent.